The design of a drug delivery system for the selective targeting of HIV- infected hosts is proposed, involving the synthesis and exploitation of small molecule inhibitors of the HIV gp120-human CD4 interaction. The system of drug delivery involves the preparation of micelles as drug delivery vehicles derived from the aggregation of amphiphilic block copolymers. Construction of the micelle involves attachment of a small molecule gp120-CD4 inhibitor with a high affinity for the HIV gp120 glycoprotein to the hydrophilic polymer block. Aggregation of the modified polymer strands should yield a micelle that incorporates gp120- CD4 inhibitors covalently attached to the micelle surface. The drug delivery micelle should be selective for HIV-infected hosts by virtue of the gp120-CD4 inhibitor's affinity for gp120, the HIV glycoprotein which is expressed on the surface of infected T-cells. Preparation of a gp120-CD4 inhibitor involves the synthesis of the tri(guanidine) alkaloid Batzelladine A, whose role as a potential gp120 recognition element in the proposed drug delivery process will be investigated. Key features of the synthesis include: (1) a novel tris(annulation) strategy employing acyl-guanidine-iminium intermediates to form the tricyclic core of the natural product from carbodiimide precursors, and (2) a convergent annulation reaction involving the coupling of a-diazoesters with N-acylthioamides to form the bicyclic core of the target. Preparation of the block-copolymer for micelle construction involves the synthesis of poly(ethylene oxide)-poly(b-benzyl-L-aspartate) block copolymer, whose size, stability and drug housing capacity present an optimal system with which to investigate selective drug delivery for HIV therapy. This research program not only investigates novel strategies for polycyclic guanidine formation, but also defines a new function for small-molecule gp120-CD4 inhibitors as HIV viral recognition elements in drug delivery and therefore has the potential to enhance both potency and selectivity in a wide range of HIV drug therapies.